Gene Interaction Implicated in Cystic Fibrosis Severity

February 25, 2008

Low expression of the mannose-binding lectin 2 (MBL2) gene appears to increase cystic fibrosis severity in part due to its association with Pseudomonas aeruginosa infection at a younger age, and MBL2's effects are increased in patients with a high-producing genotype of transforming growth factor beta 1 (TGFB1), according to a report published online Feb. 21 in the Journal of Clinical Investigation.

MONDAY, Feb. 25 (HealthDay News) -- Low expression of the mannose-binding lectin 2 (MBL2) gene appears to increase cystic fibrosis severity in part due to its association with Pseudomonas aeruginosa infection at a younger age, and MBL2's effects are increased in patients with a high-producing genotype of transforming growth factor beta 1 (TGFB1), according to a report published online Feb. 21 in the Journal of Clinical Investigation.

Ruslan Dorfman, Ph.D., of the Hospital for Sick Children in Toronto, Ontario, Canada, and colleagues analyzed data from 1,019 pediatric Canadian cystic fibrosis patients. The researchers divided patients into high-, intermediate- and low-expression of MBL2, which is involved in phagocytosis of bacteria and cytokine secretion.

MBL2 deficiency was significantly associated with median age of first P. aeruginosa infection (high = 8 years, intermediate = 7 years, low = 4.4 years). The effect of MBL2 was more pronounced in patients with high-producing genotypes of TGFB1; TGF-α1 is a growth factor with a role in inflammation. MBL2 deficiency was also associated with faster decline in lung function, especially in those with the high-producing TGFB1 genotype.

"Genetic testing for MBL2 and TGFB1 variants may permit early identification of at-risk patients either at diagnosis or through newborn screening. This would allow physicians to closely monitor these subjects and give consideration to more aggressive efforts to prevent early onset of bacterial infections. Knowledge of specific modifier genotypes would also permit more accurate patient stratification for entry into therapeutic clinical trials," the authors write.

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